SiO2-layered double hydroxide microspheres and methods of making them

ABSTRACT

Porous particles comprising an active ingredient and a coating exhibiting greater dissolution rate in aqueous media than in alcoholic media are disclosed. A process for the manufacture of the particles is also disclosed, as well as tamper-proof particles and solid dosage forms comprising the coated particles. The differential solubility characteristics of the particle coating allow the particles to be incorporated into abuse-deterrent medicaments.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a divisional of U.S. patent application Ser. No.15/541,655, filed Jul. 5, 2017, which is a national stage entry under 35U.S.C. § 371 of PCT International Application No. PCT/GB2016/050024,filed Jan. 6, 2016, which claims priority to United Kingdom PatentApplication No. 1500115.9, filed Jan. 6, 2015, the entire disclosures ofwhich are expressly incorporated by reference herein.

The present invention relates to new SiO₂-layered double hydroxide (LDH)microspheres and to methods of making the same.

Layered double hydroxides (LDHs) are a class of compounds which comprisetwo or more metal cations and have a layered structure. A review of LDHsis provided in Structure and Bonding; Vol. 119, 2005 Layered DoubleHydroxides ed. X Duan and D. G. Evans. The hydrotalcites, perhaps themost well-known examples of LDHs, have been studied for many years. LDHscan intercalate anions between the layers of the structure.

Core shell particles are described in the literature by “core@shell”(for example by Teng et al., Nano Letters, 2003, 3, 261-264, or by“core/shell” (for example J. Am. Chem Soc., 2001, 123, pages 7961-7962).We have adopted the “core@shell” nomenclature as it is emerging as themore commonly accepted abbreviation.

SiO₂/LDH core-shell microspheres are described by Shao et al, Chem.Mater. 2012, 24, pages 1192-1197. Prior to treatment with a metalprecursor solution, the SiO₂ microspheres are primed by dispersing themin an Al(OOH) primer sol for two hours with vigorous agitation followedby centrifuging, washing with ethanol and drying in air for 30 minutes.This priming treatment of the SiO₂ microspheres was repeated 10 timesbefore the SiO₂ spheres thus coated with a thin Al(OOH) film wereautoclaved at 100° C. for 48 hours in a solution of Ni(NO₃)₂.6H₂O andurea. Hollow SiO₂—NiAl-LDH microspheres obtained by this process werereported as exhibiting excellent pseudocapacitance performance.Unfortunately, the requirement for the Al(OOH) priming of the SiO₂surface, prior to LDH growth, makes this process unsuitable for use onan industrial scale.

Chen et al, J. Mater. Chem. A, 1, 3877-3880 describes the synthesis ofSiO₂@MgAl-LDHs having use in the removal of pharmaceutical pollutantsfrom water. The synthesis described comprises coprecipitating LDH from ametal precursor solution containing the SiO₂ microspheres followed byultrasound assisted direct growth of LDH nanosheets on the surface ofthe SiO₂ microspheres. Unfortunately, the reported method does not allowthe morphology of the surface LDHs to be tuned and the surface area ofthe product SiO₂@LDHs is not high.

It is an object of the present invention to provide a facile method ofmaking SiO₂@LDH microspheres which overcomes drawbacks of the prior art,which in particular does not require a step of initially forming anAl(OOH) film on the SiO₂ surface prior to treatment with the metalprecursor solution or the requirement for ultrasound assistance inachieving LDH growth on the SiO₂ surface. It is also an object of thepresent invention to provide SiO₂@LDHs wherein the thickness, size andmorphology of the LDH layer can each be tuned easily for differentapplications. It is yet a further object of the present invention toprovide SiO₂@LDHs that have high surface area.

This object is achieved by a method of making silica-layered doublehydroxide microspheres having the general formula I(SiO₂)_(p)@{[M^(z+) _((1-x))M′^(y+) _(x)(OH)₂]^(a+)(X^(n−))_(a/n).bH₂O.c(AMO-solvent)}_(q)  (I)wherein,M^(z+) and M′^(y+) are two different charged metal cations;z=1 or 2;y=3 or 4;0<x<0.9;b is 0 to 10;c is 0 to 10;p>0,q>0;X^(n−) is an anion; with n>0 (preferably 1-5)a=z(1−x)+xy−2; andthe AMO-solvent is an 100% aqueous miscible organic solvent;which method comprises the steps:

-   (a) contacting silica microspheres and a metal ion containing    solution containing metal ions M^(z+) and M′^(y+) in the presence of    a base and anion solution;-   (b) collecting the product; and-   (c) optionally treating the product with AMO-solvent and recovering    the solvent treated material.

According to a further aspect of the invention, there is provided asilica-layered double hydroxide microsphere or a plurality thereofobtained, directly obtained or obtainable by a process defined herein.

A silica-layered double hydroxide microsphere is known to comprise asilica microsphere having solid LDH attached to its surface. Such amaterial, denoted as SiO₂@LDH, may be a core-shell material where theSiO₂ microsphere is a solid sphere, a yolk-shell material where the SiO₂microsphere comprises an outer shell and a smaller SiO₂ sphere containedwithin the outer shell wherein there is a hollow portion between thesmaller sphere and the inner surface of the outer shell, or a hollowshell material wherein the SiO₂ microsphere has a hollow interior.

In an embodiment, the process does not include a step of growing the LDHon the SiO₂ surface using ultrasound.

The SiO₂ microspheres used in the preparation of the SiO₂@LDHmicrospheres according to the invention may be solid, yolk-shell orhollow microspheres and are commercially-available in a variety of sizes(diameters). However, SiO₂ microspheres may be prepared by a modifiedStöber process involving ammonia catalysed hydrolysis and condensationof tetraethylorthosilicate using ethanol as solvent andcetyltrimethylammonium bromide as surfactant porogen, as is well knownin the art.

In an embodiment, the silica microspheres do not contain any iron.

In another embodiment, the silica microspheres comprise greater than 75%w/w SiO₂. Suitably, silica microspheres comprise greater than 85% w/wSiO₂. More suitably, the silica microspheres comprise greater than 95%w/w SiO₂. Most suitably, the silica microspheres comprise greater than98% w/w SiO₂.

In another embodiment, the silica microspheres consist essentially ofSiO₂.

In another embodiment, the silica microspheres consist of SiO₂.

In another embodiment, the SiO₂ microspheres have an average diameter ofbetween 0.15 μm and 8 μm. Suitably, the SiO₂ microspheres have anaverage diameter of between 0.15 μm and 2 μm. More suitably, the SiO₂microspheres have an average diameter of between 0.15 μm and 1 μm. Mostsuitably, the SiO₂ microspheres have an average diameter of between 0.2μm and 0.8 μm.

The LDH nanosheets grown on the surface of the SiO₂ microspherescomprise, and preferably consist of, LDH represented by the generalformula I[M^(z+) _(1-x)M′^(y+) _(x)(OH)₂]^(a+)(X^(n−))_(a/n).bH₂O.c(AMO-solvent)  (I),wherein M^(z+) and M′⁺ are different charged metal cations; z=1 or 2;y=3 or 4; 0<x<0.9; b=0-10; c=0-10, X^(n−) is an anion, n is the chargeon the anion, n>0 (preferably 1-5); a=z(1−x)+xy−2; and AMO-solvent is an100% aqueous miscible organic solvent.

As stated above, M^(z+) and M′^(y+) are different charged metal cations.Having regard to the fact that z=1 or 2, M will be either a monovalentmetal cation or a divalent metal cation. When z=1, M is either a singlemonovalent metal cation or two or more different monovalent metalcations. When z=2, M is either a single divalent metal cation or two ormore different divalent metal cations. In an embodiment, z=2, i.e. M isone or more divalent metal cations. M′, in view of the fact that y=3 or4, will be a trivalent metal cation or a tetravalent metal cation. Whenz=3, M′ is either a single trivalent metal cation or two or moredifferent trivalent metal cations. When z=4, M′ is either a singletetravalent metal cation or two or more different tetravalent metalcations. In an embodiment, y=3, i.e. M′ is one or more trivalent metalcations.

A preferred example of a monovalent metal, for M, is Li. Examples ofdivalent metals, for M, include Ca, Mg, Zn, Fe, Co, Cu and Ni andmixtures of two or more of these. Preferably, the divalent metal M, ifpresent, is Ca, Ni or Mg. Examples of metals, for M′, include Al, Ga,In, Y and Fe. Preferably, M′ is a trivalent cation, for example Al.Preferably, the LDH will be a Li—Al, an Mg—Al or a Ca—Al LDH.

The anion X^(n−) in the LDH is any appropriate inorganic or organicanion. Examples of anions that may be used, as X^(n−), in the LDHinclude carbonate, hydroxide, nitrate, borate, sulphate, phosphate andhalide (F⁻, Cl⁻, Br⁻, I⁻) anions. Preferably, the anion X^(n−), isselected from CO₃ ²⁻, NO₃ ⁻ and Cl⁻.

The AMO-solvent is any aqueous miscible organic solvent, i.e. a solventwhich is 100% miscible with water. Examples of suitable water-miscibleorganic solvents for use in the present invention include one or more ofacetone, acetonitrile, dimethylformamide, dimethylsulfoxide, dioxane,ethanol, methanol, n-propanol, isopropanol, or tetrahydrofuran.Suitably, the water-miscible organic solvents for use in the presentinvention is selected from lower (1-3C) alkanols and acetone.Preferably, the AMO-solvent is methanol, ethanol or acetone, especiallyacetone and ethanol.

According to one preferred embodiment, the layered double hydroxides arethose having the general formula I above

in which M^(z+) is a divalent metal cation;

M′⁺ is a trivalent metal cation; and

each of b and c is a number>zero, which gives compounds optionallyhydrated with a stoichiometric amount or a non-stoichiometric amount ofwater and/or an aqueous-miscible organic solvent (AMO-solvent), such asacetone or ethanol.

Preferably, in the LDH of the above formula, M is Mg or Ca and M′ is Al.The counter anion X^(n−) is typically selected from CO₃ ²⁻, OH⁻, F⁻,Cl⁻, Br⁻, I⁻, SO₄ ²⁻, NO₃ ⁻ and PO₄ ³⁻. In a most preferred embodiment,the LDH will be one wherein M is Mg, M′ is Al and X^(n−) is CO₃ ²⁻.

In carrying out the method of the invention, preferably the SiO₂microspheres are dispersed in an aqueous solution containing the desiredanion salt, for example Na₂CO₃. A metal precursor solution, i.e. asolution combining the required monovalent or divalent metal cations andthe required trivalent cations may then be added, preferably drop-wise,into the dispersion of the SiO₂ microspheres. Preferably, the additionof the metal precursor solution is carried out under stirring. The pH ofthe reaction solution is preferably controlled within the pH range 8 to12, typically 8-11, more preferably 9 to 10.

In an embodiment, the method of the present invention does not includeammonia.

The structure of the SiO₂@LDH microspheres can be controlled by thetendency of SiO₂ to dissolve or partially dissolve at highertemperatures and higher pH values. For instance, carrying out theaddition of the metal precursor solution to the dispersion of SiO₂microspheres at room temperature and at pH 10 gives solid SiO₂@LDHparticles although by raising the temperature of the reaction solutions,for instance to 40° C., it is possible to obtain yolk shell SiO₂@LDHparticles. By carrying out the reaction at room temperature but using ahigher solution pH, e.g. pH 11, it is possible to produce hollow shellSiO₂@LDH particles.

Typically, NaOH may be used to adjust the pH of the solution.

During the reaction, the LDH produced from the metal precursor solutionreaction is formed on the SiO₂ surfaces of the microspheres asnanosheets.

It is preferred that the temperature of the metal ion containingsolution in step (a) is within a range of from 20 to 150° C. Morepreferably, from 20 to 80° C.

In a preferred embodiment, the silica-layered double hydroxidemicrospheres have specific surface area of at least 100 m²/g, preferablyat least 177 m²/g, and more preferably at least 200 m²/g, and even morepreferably at least 250 m²/g.

Suitably, the silica-layered double hydroxide microspheres comprisesolid silica mircrosphere cores and have specific surface area of atleast 100 m²/g.

Suitably, the silica-layered double hydroxide microspheres compriseyolk-shell mircrosphere cores and have specific surface area of at least100 m²/g.

Suitably, the silica-layered double hydroxide microspheres comprisehollow-shell mircrosphere cores and have specific surface area of atleast 130 m²/g.

Most preferred, the silica-layered double hydroxide microspheres have atleast one structure from hollow-shell, yolk-shell and solid core-shellstructures.

In a preferred embodiment, the silica-layered double hydroxidemicrospheres have a thickness of layered double hydroxide layer largerthan 65 nm, preferably larger than 110 nm, more preferably larger than160 nm.

The obtained solid product is collected from the aqueous medium.Examples of methods of collecting the solid product includecentrifugation and filtration. Typically, the collected solid may bere-dispersed in water and then collected again. Preferably, thecollection and re-dispersion steps are repeated twice.

The finally-obtained solid material may then be subjected to drying, forinstance, in an oven for several hours.

In the event that a product containing AMO-solvent is required, thematerial obtained after the collection/re-dispersion procedure describedabove may be washed with, and preferably also re-dispersed in, thedesired solvent, for instance acetone or ethanol. If re-dispersion isemployed, the dispersion is preferably stirred. Stirring for more than 2hours in the solvent is preferable. The final product may then becollected from the solvent and then dried, typically in an oven forseveral hours.

In an embodiment, the LDH layer is formed in situ. Suitably, the LDH isformed and coated onto the silica microspheres in situ.

The growth of LDH nanosheets on the surface of the SiO₂ microspheres is“tuneable”. That is to say, by varying the chemistry of the precursorsolution, pH of the reaction medium and the rate of addition of theprecursor solution to the dispersion of SiO₂ microspheres, the extentof, and the length and/or thickness of, the LDH nanosheets formed on theSiO₂ surface can be varied.

The production of the SiO₂@LDH microspheres according to the inventioncan be carried out as a batch process or, with appropriate replenishmentof reactants, as a continuous process.

The products of the method of the present invention where the SiO₂@LDHsare treated with solvent, i.e. the products having the formula I abovewhere c is greater than zero, are a solution to the problem underlyingthe present invention per se.

Thus, according to a further aspect, the present invention providessilica-layered double hydroxide microspheres having the formula I(SiO₂)_(p)@{[M^(z+) _((1-x))M′^(y+) _(x)(OH)₂]^(a+)(X^(n−))_(a/n).bH₂O.c(AMO-solvent)}_(q)  (I)wherein,M^(z+) and M′^(y+) are two different charged metal cations;z=1 or 2;y=3 or 4;0<x<0.9;b is 0 to 10;c is 0 to 10;p>0,q>0;X^(n−) is an anion; with n>0 (preferably 1-5)a=z(1−x)+xy−2; andAMO-solvent is an 100% aqueous miscible organic solvent.

M′ in formula I above is preferably Al.

M in formula I above is preferably Li, Mg, Ga, In, Ni, Co, Cu or Ca,more preferably Mg or Ni.

According to an embodiment, X^(n−) in formula I above is selected fromcarbonate, nitrate, borate, sulphate, phosphate, hydroxide and halideanions (F⁻, Cl⁻, Br⁻, I⁻). Preferably, the anion X^(n−) is selected fromCO₃ ²⁻, NO₃ ⁻ and Cl⁻.

According to a particularly preferred embodiment, the SiO₂@LDHmicrospheres of the invention contain LDH having the formula I above inwhich M is Mg, M′ is Al and X^(n−) is CO₃ ⁻.

The AMO-solvent in formula I above is one that is miscible in water,especially one that is 100% miscible in water. Examples of solvents thatcan be used include methanol, ethanol and acetone. According to apreferred embodiment of the invention, the solvent is ethanol oracetone.

SiO₂@LDHs according to the present invention may be used as catalystsand/or catalyst supports.

PARTICULARLY PREFERRED EMBODIMENTS

The following represent particular embodiments of the silica-layereddouble hydroxide:

-   1.1 The silica-layered double hydroxide microspheres have the    general formula I    (SiO₂)_(p)@{[M^(z+) _((1-x))M′^(y+) _(x)(OH)₂]^(a+)(X^(x−))_(a/n)    .bH₂O.c(AMO-solvent)}_(q)  (I)    -   wherein,    -   M^(z+) is selected from Li⁺, Ca²⁺, Ni²⁺ or Mg²⁺, and M′^(y+) is        Al³⁺ or Fe³⁺;    -   0<x<0.9;    -   b is 0 to 10;    -   c is 0 to 10;    -   p>0,    -   q>0;    -   X^(n−) is selected from carbonate, hydroxide, nitrate, borate,        sulphate, phosphate and halide (F⁻, Cl⁻, Br⁻, I⁻) anions; with        n>0 (preferably 1-5) a=z(1−x)+xy−2; and    -   the AMO-solvent is selected from a lower (1-3C) alkanol (e.g.        ethanol) or acetone.-   1.2 The silica-layered double hydroxide microspheres have the    general formula I    (SiO₂)_(p)@{[M^(z+) _((1-x))M′^(y+) _(x)(OH)₂]^(a+)(X^(n−))_(a/n)    .bH₂O.c(AMO-solvent)}_(q)  (I)    -   wherein,    -   M^(z+) is selected from Li⁺, Ca²⁺, Ni²⁺ or Mg²⁺, and M′^(y+) is        Al³⁺;    -   0<x<0.9;    -   b is 0 to 10;    -   c is 0 to 10;    -   p>0,    -   q>0;    -   X^(n−) is selected from CO₃ ²⁻, NO₃ ⁻ or Cl⁻; with n>0        (preferably 1-5)    -   a=z(1−x)+xy−2; and    -   the AMO-solvent is acetone or ethanol.-   1.3 The silica-layered double hydroxide microspheres have the    general formula Ia    (SiO₂)_(p)@{[M^(z+) _((1-x))Al³⁺ _(x)(OH)₂]^(a+)(X^(n−))_(a/n)    .bH₂O.c(AMO-solvent)}_(q)  (Ia)    -   wherein,    -   M^(z+) is selected from Li⁺, Ca²⁺, Ni²⁺ or Mg²⁺;    -   0<x<0.9;    -   b is 0 to 10;    -   c is 0 to 10;    -   p>0,    -   q>0;    -   X^(n−) is selected from CO₃ ²⁻, NO₃ ⁻ or Cl⁻; with n>0        (preferably 1-5)    -   a=z(1−x)+xy−2; and    -   the AMO-solvent is acetone or ethanol.-   1.4 The silica-layered double hydroxide microspheres have the    general formula Ia    (SiO₂)_(p)@{[Mg²⁺ _((1-x))Al³⁺ _(x)(OH)²]^(a+)(X^(n−))_(a/n)    .bH₂O.c(AMO-solvent)}_(q)  (Ia)    -   wherein,    -   0<x<0.9;    -   b is 0 to 10;    -   c is 0 to 10;    -   p>0,    -   q>0;    -   X^(n−) is selected from CO₃ ²⁻, NO₃ ⁻ or Cl⁻; with n>0        (preferably 1-5)    -   a=z(1−x)+xy−2; and    -   the AMO-solvent is acetone or ethanol.-   1.5 The silica-layered double hydroxide microspheres have the    general formula Ib    (SiO₂)_(p)@{[Mg²⁺ _((1-x))Al³⁺ _(x)(OH)₂]^(a+)(CO₃ ²)_(a/n)    .bH₂O.c(acetone)}_(q)  (Ib)    -   wherein,    -   0<x<0.9;    -   b is 0 to 10;    -   c is 0 to 10;    -   p>0,    -   q>0;    -   a=z(1−x)+xy−2.-   1.6 The silica-layered double hydroxide microspheres have the    general formula Ic    (SiO₂)_(0.04)@{[Mg_(0.75)Al_(0.25)(OH)₂](CO₃)_(0.125).1.34(H₂O)}_(0.05)  (Ic)-   1.7 The silica-layered double hydroxide microspheres have the    general formula Id    (SiO₂)_(0.04)@{[Mg_(0.75)Al_(0.25)(OH)₂](CO₃)_(0.125).0.29(H₂O).0.15(acetone)}_(0.05)  (Id)

Preferred, suitable, and optional features of any one particular aspectof the present invention are also preferred, suitable, and optionalfeatures of any other aspect.

FIGURES

FIG. 1 . XRD patterns showing three sizes of silica nanoparticles (a)300 nm, (b) 550 nm and (c) 800 nm.

FIG. 2 . TGA curves of differently sized silica nanoparticles (a) 800nm, (b) 550 nm and (c) 300 nm.

FIG. 3 . SEM images of 800 nm silica microspheres prepared via seededgrowth.

FIG. 4 . XRD patterns of (a) 550 nm silica microspheres, (b) LDHnano-particles and (c) SiO₂@LDH microspheres ((b) and (c) weresynthesized according to example 1).

FIG. 5 . Percentage weight loss of (a) LDH, (b) SiO₂@LDH microspheresand (c) silica nanoparticles ((a) and (b) were synthesized according toexample 1).

FIG. 6 . ²⁹Si Solid-state NMR of (a) silica microspheres and (b)SiO₂@LDH microspheres ((b) were synthesized according to example 1).

FIG. 7 . XRD patterns of SiO₂@LDH microspheres prepared at different pHconditions (a) ammonia method (example 4), (b) pH 9, (c) pH 10 and (d)pH 11 ((b)-(d): example 1).

FIG. 8 . TGA of SiO₂@LDH microspheres prepared at different pHconditions (a) pH 11, (b) pH 10, (c) ammonia method and (d) pH 9.

FIG. 9 . TEM images of SiO₂@LDH microspheres synthesized according toexample 1 except at different temperatures (a) room temperature (b) 40°C.

FIG. 10 . TGA and dTGA curves of SiO₂@LDH microspheres preparedaccording to example 1 except at different temperature (a) roomtemperature and (b) 40° C., (i) TGA curve, (ii) dTGA curve.

FIG. 11 . Solid state NMR (a)²⁹Si (b)²⁷Al. SiO₂ @ LDH prepared accordingto example 1 except at different temperature (i) at room temperature(ii) at 40° C.

FIG. 12 . XRD patterns of SiO₂@LDH microspheres prepared with differentMg:Al ratios (a) 1:1 (example 2), (b) 3:1 (example 3).

FIG. 13 . XRD patterns of SiO₂@LDH microspheres prepared according toexample 1 (a) conventional water washing (b) acetone washing.

FIG. 14 . TGA of SiO₂@LDH microspheres prepared according to example 2(a) conventional water washing (b) acetone washing.

FIG. 15 . TEM image of SiO₂@LDH microspheres with different ratio ofMg/Al (a) 1:1 (example 2), (b) 2:1 (example 1) and (c) 3:1 (example 3).

FIG. 16 . TEM image of SiO₂@LDH microspheres according to example 1except with different size of silica (a) 300 nm, (b) 550 nm and (c) 800nm.

FIG. 17 . TEM image of SiO₂@LDH microspheres with different morphology(a) solid (example 1), (b) yolk-shell (example 1 at 40° C.) and (c)hollow (example 1 at pH 11).

FIG. 18 . XRD patterns of SiO₂@AMO-LDH with an Mg:Al=3:1 (a) pH=10 androom temperature (b) pH=10 and 40° C. (c) pH=11 and 40° C.

FIG. 19 . XRD patterns of SiO₂@AMO-LDH with Mg:Ni:Al=2.7:0.3:1 (a) pH=10and room temperature (b) pH=10 and 40° C. (c) pH=11 and 40° C.

FIG. 20 . XRD patterns of SiO₂@AMO-LDH with an Mg:Al:Fe=3:0.9:0.1 (a)pH=10 and room temperature (b) pH=10 and 40° C. (c) pH=11 and 40° C.;

FIG. 21 . TEM image of SiO₂@AMO LDH microspheres according to examples 5and 7 at pH=10 and room temperature (a) Mg:Al=3:1 (b)Mg:Al:Fe=3:0.9:0.1.

FIG. 22 . TEM image of SiO₂@AMO-LDH with Mg:Ni:Al=2.7:0.3:1 microsphereswith different morphology according to example 6 (a) pH=10 and roomtemperature (b) pH=10 and 40° C. (c) pH=11 and 40° C.

EXPERIMENTAL METHODS

1. General Details

1.1 Powder X-Ray Diffraction

Powder X-ray diffraction (XRD) data were collected on a PANAnalyticalX'Pert Pro diffractometer in reflection mode and a PANAnalyticalEmpyrean Series 2 at 40 kV and 40 mA using Cu Kα radiation (α1=1.54057Å, α2=1.54433 Å, weighted average=1.54178 Å). Scans were recorded from5°≤0≤70° with varying scan speeds and slit sizes. Samples were mountedon stainless steel sample holders. The peaks at 43-44° are produced bythe XRD sample holder and can be disregarded.

1.2 Thermogravimetric Analysis

Thermogravimetric analysis (TGA) measurements were collected using aNetzsch STA 409 PC instrument. The sample (10-20 mg) was heated in acorundum crucible between 30° C. and 800° C. at a heating rate of 5° C.min-1 under a flowing stream of nitrogen.

1.3 Solid State NMR Spectroscopy

²⁹Si and ²⁷Al MAS NMR spectra were recorded on a Varian Chemagnetics CMXInfinity 200 (4.7 T). Samples were packed in 7.5 mm zirconia rotors. Adouble resonance MAS probe was used for all measurements and a MAS rateof 4 kHz for ²⁹Si, whereas MAS rate of 6 kHz was used for ²⁷Al. ²⁷Al MASNMR spectra were acquired with a single pulse excitation applied using ashort pulse length (0.7 μs). Each spectrum resulted from 2000 scansseparated by 1 s delay. The ²⁷Al chemical shifts are referenced to anaqueous solution of Al(NO₃)₃ (δ=0 ppm). In order to obtain thequantitative ²⁹Si DPMAS NMR spectra, 5000 transients were typicallyacquired with an acquisition time of 68 ms (1024 data points zero filledto 16K) and recycle delay of 30 s. All ²⁹Si spectra were externallyreferenced to kaolinite (taken to be at δ=−91.7 ppm on a scale whereδ(TMS)=0 ppm) as a secondary reference.

1.4 Transmission Electron Microscopy

Transmission Electron Microscopy (TEM) analysis was performed on a JEOL2100 microscope with an accelerating voltage of 200 kV. Particles weredispersed in water or ethanol with sonication and then cast onto coppergrids coated with carbon film and left to dry.

1.5 Scanning Electron Microscopy

Scanning Electron Microscopy (SEM) analysis was performed on a JEOL JSM6610 scanning electron microscope. Particles were dispersed in water andcast onto a clean silica wafer. Before imaging, the samples were coatedwith a thin platinum layer to prevent charging and to improve the imagequality. Energy dispersive X-ray spectroscopy (EDX), also carried out onthis instrument, was used to determine the relative quantities ofconstituent elements on the surface of the sample.

1.6 Brunauer-Emmett-Teller Surface Area Analysis

Brunauer-Emmett-Teller (BET) specific surface areas were measured fromthe N₂ adsorption and desorption isotherms at 77 K collected from aQuantachrome Autosorb surface area and pore size analyser.

Example 1

Silica spheres (100 mg, 550 nm) were dispersed in deionised water (20mL) using ultrasound treatment. After 30 min., Na₂CO₃ (0.96 mmol) wasadded to the solution and a further 5 min of sonication was carried outto form solution A. Next an aqueous solution (19.2 mL) containingMg(NO₃)₂.6H₂O (0.96 mmol) and Al(NO₃)₃.9H₂O (0.48 mmol) was added at arate of 60 mL/h to solution A under vigorous stirring at roomtemperature. The pH of the reaction solution was controlled to be 10with the addition of 1 M NaOH. The obtained solid was collected withcentrifugation at 4000 rpm for 5 min and then re-dispersed in deionisedwater (40 mL) and stirred for 1 h. The collection and re-dispersion wererepeated twice. Afterward, the solid was washed with acetone (40 mL) andthen re-dispersed in acetone (40 mL) and left to stir overnight. Thesolid was then dried under vacuum.

The SiO₂@LDH obtained in this Example, before the treatment withacetone, has the formula:—(SiO₂)_(0.04)@{[Mg_(0.75)Al_(0.25)(OH)₂](CO₃)_(0.125).1.34(H₂O)}_(0.05)

The SiO₂@AMO-LDH, obtained after acetone treatment, has the formula:—(SiO₂)_(0.04)@{[Mg_(0.75)Al_(0.25)(OH)₂](CO₃)_(0.125).0.29(H₂O).0.15(acetone)}_(0.05)

Yolk shell particles were obtained by carrying out the addition of theaqueous solution containing the Mg(NO₃)₂.6H₂O and Al(NO₃)₃.9H₂O at 40°C. and pH10.

Hollow shell particles were obtained by carrying out the addition of theaqueous solution containing Mg(NO₃)₂.6H₂O and Al(NO₃)₃.9H₂O at roomtemperature but at pH11.

Surface Area Analysis

The solid SiO₂@LDH, the yolk shell SiO₂@LDH and the hollow shellSiO₂@LDH prepared as described above but without acetone treatment weresubjected to Brunauer-Emmett-Teller (BET) surface area analysis.

The N₂ BET surface areas of the products were:

BET surface area (m²g⁻¹) Solid (i.e. core-shell) SiO₂@LDH 107 Yolk-shellSiO₂@LDH 118 Hollow-shell SiO₂@LDH 177

The BET surface areas reported above may be favourably compared to thoseof SiO₂@LDHs prepared according to (A) Shao et a. Chem. Mater. 2012, 24,pages 1192-1197 and to those of SiO₂@LDHs prepared according to (B) Chenet a. J. Mater. Chem. A, 1, 3877-3880.

(A) SiO₂ Microspheres Pre-Treated with Al(OOH).

Product SiO₂@NiAl LDH. BET surface area (m²g⁻¹) Solid (i.e. core-shell)SiO₂ microspheres 42.3 Yolk-shell SiO₂@LDH microspheres 68 Hollow-shellSiO₂@LDH microspheres 124(B) SiO₂ Microspheres—No Pre-Treatment—Ammonia Method.

Product SiO₂@LDH. BET surface area (m²g⁻¹) Solid (i.e. core-shell)SiO₂@LDH microspheres 61

Core-shell SiO₂@LDHs were prepared according to the procedures describedin Example 1 and in the Examples 2 and 3 below having differentthicknesses of LDH layer. The ratio of Mg/Al was varied to control thethickness of the LDH layer. A Mg:Al ratio of 1:1 was found to give anLDH layer of thickness 65 nm, a ratio of 2:1 was found to give an LDHlayer of thickness 110 nm and a layer of thickness of 160 nm wasobtained using a Mg:Al ratio of 3:1. TEM images are shown in FIG. 15 .Core-shell SiO₂@LDHs were also prepared according to the proceduredescribed in Example 1 above using different sized SiO₂ microspheres,300 nm, 550 nm and 800 nm. TEM images are shown in FIG. 16 . TEM imagesof the SiO₂@LDHs produced with different morphology (a) solid (Example1), (b) yolk shell (Example 1 at 40° C.) and (c) hollow (Example 1 atpH11), as described above, are shown in FIG. 17 .

Example 2

In order to obtain a 1:1 Mg:Al LDH, the procedure described above inExample 1 was repeated with the exception that an aqueous solution (19.2mL) containing Mg(NO₃)₂.6H₂O (0.72 mmol) and Al(NO₃)₃.9H₂O (0.72 mmol)was added at a rate of 60 mL/h to solution A under vigorous stirring.

Example 3

In order to obtain a 3:1 Mg:Al LDH, the procedure described above inExample 1 was repeated with the exception that an aqueous solution (19.2mL) containing Mg(NO₃)₂.6H₂O (1.08 mmol) and Al(NO₃)₃.9H₂O (0.36 mmol)was added at a rate of 60 mL/h to solution A under vigorous stirring.

The XRD patterns of the SiO₂@LDH samples prepared with Mg:Al ratios of1:1 (Example 2) and 3:1 (Example 3) are shown in FIG. 12 .

Example 4

The silica@LDH particles were synthesised via the coprecipation method.Silica spheres (100 mg, 550 nm) were dispersed in deionised water (20mL) using ultrasound treatment. After 30 min, the anion salt (0.96mmol), Na₂CO₃, was added to the solution containing ammonia (0.8 mL,35%) and a further 5 min of sonication was carried out to form solutionA. Next an aqueous solution (19.2 mL) containing Mg(NO₃)₂.6H₂O) (0.96mmol) and Al(NO₃)₃.9H₂O (0.48 mmol) was added at a rate of 60 mL/h tosolution A under vigorous stirring. The obtained solid was collectedwith centrifugation at 4000 rpm for 5 min and then re-dispersed indeionised water (40 mL) and stirred for 1 h. The collection andre-dispersion were repeated twice. Afterward, the solid was washed withacetone (40 mL) and then re-dispersed in acetone (40 mL) and left tostir overnight. The solid was then dried under vacuum. The suspensionwas then dried under vacuum for materials characterisation.

The features disclosed in the foregoing description, in the claims aswell as in the accompanying drawings, may both separately and in anycombination thereof be material for realizing the invention in diverseforms thereof.

Example 5

In order to obtain Silica@AMO-LDHs in Mg:Al=3:1. Synthesise theSilica@LDH particles by using the co-precipitation method, dispersesilica spheres (100 mg) in the deionised water (20 mL) by usingultrasound treatment for 30 min, add the anion salt Na₂CO₃ (0.96 mmol)in the solution and further treat by ultrasound for 5 min, the finallysolution named A. Then add an aqueous solution (19.2 mL) containing(1.08 mmol) Mg²⁺ and (0.36 mmol) Al³⁺ in the solution A at the rate of60 mL/h with vigorous stirring. The pH of the reaction solution iscontrolled with the addition of 1 M NaOH by an autotitrator. And themorphology of Silica@LDH is controlled by pH and temperature. Theobtained solid is collected with centrifugation at 5000 rpm for 5 minand then re-dispersed in deionised water (40 mL) and stir for 1 h, thewashing need repeated twice. Before final isolation, the solid is washedwith acetone (40 mL) and left to stir over night, and the suspension isthen dried under vacuum

Example 6

In order to obtain Silica@AMO-LDHs in Mg:Ni:Al=2.7:0.3:1. The Silica@LDHparticles will be synthesized by using the co-precipitation method,disperse silica spheres (100 mg) in the deionised water (20 mL) by usingultrasound treatment for 30 min, add the anion salt Na₂CO₃ (0.96 mmol)in the solution and further treat by ultrasound for 5 min, the finallysolution named A. Then add an aqueous solution (19.2 mL) containing(0.972 mmol) Mg²⁺, (0.108 mmol) Ni²⁺ and (0.36 mmol) Al³⁺ in thesolution A at the rate of 60 mL/h with vigorous stirring. The pH of thereaction solution is controlled with the addition of 1 M NaOH by anautotitrator. As followed the morphology of Silica@LDH is controlled bypH and temperature. The obtained solid is collected with centrifugationat 5000 rpm for 5 min and then re-dispersed in deionised water (40 mL)and stir for 1 h, the washing need repeated twice. Before finalisolation, the solid is washed with acetone (40 mL) and left to stirover night, and the suspension is then dried under vacuum.

Example 7

In order to obtain Silica@AMO-LDHs in Mg:Al:Fe=3:0.9:0.1. The Silica@LDHparticles synthesise using the co-precipitation method, disperse silicaspheres (100 mg) in the deionised water (20 mL) by using ultrasoundtreatment for 30 min, add the anion salt Na₂CO₃ (0.96 mmol) in thesolution and further treat by ultrasound for 5 min, the finally solutionnamed A. Then add an aqueous solution (19.2 mL) containing (1.08 mmol)Mg²⁺, (0.324 mmol) Al³⁺ and (0.036 mmol) Fe³⁺ in the solution A at therate of 60 mL/h with vigorous stirring. The pH of the reaction solutionis controlled with the addition of 1 M NaOH by an autotitrator. Asfollowed the morphology of Silica@LDH is controlled by pH andtemperature. The obtained solid is collected with centrifugation at 5000rpm for 5 min and then re-dispersed in deionised water (40 mL) and stirfor 1 h, the washing need repeated twice. Before final isolation, thesolid is washed with acetone (40 mL) and left to stir over night, andthe suspension is then dried under vacuum

The invention claimed is:
 1. Silica-layered double hydroxidemicrospheres having the formula I below(SiO₂)_(p)@{[M^(z+) _((1-x))M′^(y+) _(x)(OH)₂]^(a+)(X^(n−))_(a/n).bH₂O.c(AMO-solvent)}_(q)  (I) wherein, M^(z+) and M′^(y+) are twodifferent charged metal cations; z=1 or 2; y=3 or 4; 0<x<0.9; b is 0 to10; c is 0 to 10; p>0, q>0; X^(n−) is an anion; with n>0; a=z(1−x)+xy−2;and AMO-solvent is an 100% aqueous miscible organic solvent, wherein thesilica-layered double hydroxide microspheres each comprise a SiO₂microsphere having solid layered double hydroxide attached to itssurface, and wherein: A. the silica-layered double hydroxidemicrospheres are core-shell materials wherein the SiO₂ microsphere is asolid sphere, and wherein the specific surface area of the core-shellmaterials is at least 100 m²/g, or B. the silica-layered doublehydroxide microspheres are yolk-shell materials wherein the SiO₂microsphere comprises an outer shell and a smaller SiO₂ sphere containedwithin the outer shell, wherein there is a hollow portion between thesmaller sphere and the inner surface of the outer shell, and wherein thespecific surface area of the yolk-shell materials is at least 100 m²/g,or C. the silica-layered double hydroxide microspheres are hollow shellmaterials wherein the SiO₂ microsphere has a hollow interior, andwherein the hollow shell materials have a specific surface area of atleast 130 m²/g; and wherein the silica-layered double hydroxidemicrospheres have a thickness of layered double hydroxide layer largerthan 110 nm.
 2. Silica-layered double hydroxide microspheres accordingto claim 1, wherein M′ is one or more trivalent cations and M is one ormore divalent cations.
 3. Silica-layered double hydroxide microspheresaccording to claim 1, wherein M′ is Al or Fe.
 4. Silica-layered doublehydroxide microspheres according to claim 1, wherein M is Ca, Cu, Ni orMg.
 5. Silica-layered double hydroxide microspheres according to claim1, wherein X^(n−) is carbonate, hydroxide, nitrate, borate, sulphate,phosphate, halide or a mixture of two or more thereof.
 6. Silica-layereddouble hydroxide microspheres according to claim 1, wherein X^(n−) isCO₃ ²⁻, Cl⁻, NO₃ ⁻ or a mixture of two or more thereof. 7.Silica-layered double hydroxide microspheres according to claim 1,wherein M′ is Al or Fe, M is Ca, Cu, Ni or Mg, and X^(n−) is CO₃ ²⁻,Cl⁻, NO₃ ⁻ or a mixture of two or more thereof.
 8. Silica-layered doublehydroxide microspheres according to claim 1, wherein M is Mg, M′ is Aland X^(n−) is CO₃ ²⁻.
 9. Silica-layered double hydroxide microspheresaccording to claim 1, wherein the silica microspheres comprise greaterthan 95% w/w SiO₂.
 10. Silica-layered double hydroxide microspheresaccording to claim 9, wherein M′ is Al or Fe, M is Ca, Cu, Ni or Mg, andX^(n−) is CO₃ ²⁻, Cl⁻, NO₃ ⁻ or a mixture of two or more thereof. 11.Silica-layered double hydroxide microspheres according to claim 9,wherein M is Mg, M′ is Al and X^(n−) is CO₃ ²⁻.
 12. Silica-layereddouble hydroxide microspheres according to claim 1, wherein the silicamicrospheres do not contain iron.
 13. Silica-layered double hydroxidemicrospheres according to claim 12, wherein M′ is Al or Fe, M is Ca, Cu,Ni or Mg, and X^(n−) is CO₃ ²⁻, Cl⁻, NO₃ ⁻ or a mixture of two or morethereof.
 14. Silica-layered double hydroxide microspheres according toclaim 12, wherein M is Mg, M′ is Al and X^(n−) is CO₃ ²⁻. 15.Silica-layered double hydroxide microspheres according to claim 1,wherein c is greater than zero.
 16. Silica-layered double hydroxidemicrospheres according to claim 15, wherein the AMO-solvent is acetone,ethanol, methanol or a mixture of two or more thereof. 17.Silica-layered double hydroxide microspheres according to claim 16,wherein M′ is Al or Fe, M is Ca, Cu, Ni or Mg, and X^(n−) is CO₃ ²⁻,Cl⁻, NO₃ ⁻ or a mixture of two or more thereof.
 18. Silica-layereddouble hydroxide microspheres according to claim 17, wherein the silicamicrospheres comprise greater than 95% w/w SiO₂.
 19. Silica-layereddouble hydroxide microspheres according to claim 16, wherein M is Mg, M′is Al and X^(n−) is CO₃ ²⁻.
 20. Silica-layered double hydroxidemicrospheres according to claim 19, wherein the silica microspheres donot contain iron.